1.3.2 Antigen Recognition in the Adaptive Immune System

Question 1

What are some basic characteristics of BCRs and TCRs?

Answer 1

Each BCR/TCR recognizes one antigen with high affinity and ALL BCRs/TCRs on a given cell are identical

Question 2

What is an antigen?

Answer 2

Any substance that can bind specifically to an antibody or TCR

Question 3

Immunogen?

Answer 3

An antigen capable of eliciting an immune response

Question 4

What is an epitope/antigenic determinant?

Answer 4

Portion of the antigen that binds to the Ab or TCR

Question 5

What does the term monoclonal mean?

Answer 5

A lymphocyte mediated immune response in which all involved lymphocytes are derived from a single clone

Question 6

What does the term polyclonal mean?

Answer 6

a lymphocyte mediated immune response in which all involved are derived from multiple clones

Question 7

What is cross-reactivity?

Answer 7

The binding of an antigen by an antibody or TCR specific for another antigen

Question 8

What is an example of cross-reactivity?

Answer 8

Ex. Antibodies against Streptococcal M protein can cross react with myocardial antigens

Question 9

Dimer – alpha/beta – mostly in lymphoid tissue, Transmembrane proteins, One ligand-binding region are characteristics of a TCR or BCR?

Answer 9

TCR

Question 10

Presented on MHC and is primarily peptides and can be anywhere within the protein and must be sequential amino acids are characteristics of the antigens presented to TCRs or BCRs?

Answer 10

TCRs

Question 11

Dimer of dimers – two heavy and two light chains, transmembrane or soluble, two ligand binding regions are characteristic of a TCR or BCR?

Answer 11

BCR

Question 12

Native antigen which can be proteins, lipids, polysaccharides, or DNA and must be on the surface of Ag and can be sequential residues or residue brought together by conformation are characteristics of the antigens presented to TCRs or BCRs?

Answer 12

BCR

Question 13

What is a super-antigen?

Answer 13

Microbial antigen that cross-link TCR and MHC independently of antigen specificity, outside of the peptide binding groove

Question 14

What can a super antigen result in?

Answer 14

This leads to poly-clonal T cell responses which can lead to a cytokine storm

Question 15

What are some possible sources of super antigens?

Answer 15

Staphylococcus, streptococcus, mycoplasma, Epstein Barr virus, and Rabies

Question 16

Determination of whether a BCR is soluble or membrane bound is determined by what?

Answer 16

splicing of the mRNA

Question 17

What are the two chains of the BCR?

Answer 17

Heavy and light chain

Question 18

What are the two regions of the heavy and light chain?

Answer 18

Variable and constant regions

Question 19

The complementary determining region is also known as what?

Answer 19

The hypervariability region

Question 20

The Fab region is?

Answer 20

The Ag-binding fragment

Question 21

The FC region is?

Answer 21

Crystallizable

Question 22

What provides the structure and flexibility of the hinge region?

Answer 22

Proline-rich regions provide the structure while the flexibility is provided by high levels of glycine

Question 23

What is the importance of the flexibility of BCRs?

Answer 23

The hinge region can flex to allow binding Ag in different conformations. Binding Ag also induces conformation changes in the constant region enabling binding to complement or Fc receptors

Question 24

What is the biggest antibody isotype?

Answer 24

IgM - Pentamer

Question 25

What antibodies are rare in sera?

Answer 25

IgD and IgE

Question 26

What antibody is most abundant in sera?

Answer 26

IgG

Question 27

Antibody multimers are connected together by?

Answer 27

J-chains

Question 28

What is affinity?

Answer 28

The strength with which a ligand interacts with a binding site

Question 29

What is avidity?

Answer 29

The strength of a protein-protein interaction when multiple binding sites are possible

Question 30

The heavy chain of a BCR genome contains what regions?

Answer 30

Variable (V), Diversity (D), and Joining (J)

Question 31

What is the process of generating B cell diversity in the DNA?

Answer 31

Genomic DNA is re-arranged yielding different V(D)J conformations. D to J recombination occurs first which is followed by V to DJ. This process is mediated by V(D)J recombinase

Question 32

RAG-1 and RAG-2 have what role?

Answer 32

These mediate combinatorial diversity

Question 33

What is the role of TdT?

Answer 33

mediates junctional diversity by addition and subtraction of nucleotides at the coding joint

Question 34

What are the components of the pro-B cell?

Answer 34

This cell expresses transmembrane Ig-alpha/beta

Question 35

What are the components of the Pre-B cell?

Answer 35

This cell expresses heavy chain and surrogate light chain on the surface

Question 36

What are the components of the Immature B cell?

Answer 36

have a heavy and light chain are ready for cross-linking for activation or death

Question 37

What is allelic exclusion?

Answer 37

Recombination continues on both alleles until successful recombination or cell runs out of coding sequence. Successful recombination of one allele inhibits rearrangement of opposite allele

Question 38

What is re-activated with progression from the Pre-BCR to the BCR?

Answer 38

Re-expression of RAG-1/2 but not TdT

Question 39

What is positive selection of the BCR?

Answer 39

Can the newly formed BCR be expressed?

Question 40

What is the process of negative selection of the BCR?

Answer 40

does the new BCR bind self-antigen with high affinity

Question 41

What is BCR editing?

Answer 41

If the BCR binds self-antigen then the auto specific B cell undergoes a second light chain rearrangement, after second light chain is added it will undergo another round of selection

Question 42

What is clonal deletion?

Answer 42

if BCR editing does not succeed, cells will undergo apoptosis; cells that undergo positive selection become mature naïve B cells

Question 43

What is the process of generating the pre-TCR?

Answer 43

Genomic DNA is re-arranged yielding different V(D)J conformations. D to J recombination occurs first which is followed by V to DJ. This process is mediated by V(D)J recombinase

Question 44

Are RAG-1/2 and TdT used in TCR maturation?

Answer 44

Yes

Question 45

What are T cell receptor excision circles (TRECs) and what are they used for?

Answer 45

circular DNA formed by the genomic rearrangement that occurs during V(D)J recombination. They are measured by qPCR and can be used in a diagnostic setting to determine thymic output after HSCT.

Question 46

What is a double negative T cell?

Answer 46

this is where the alpha/beta or gamma/delta lineage is decided; and CD3 Pre-TCR is expressed. There is no CD4 or CD8 expressed

Question 47

What is a double positive T cell?

Answer 47

TCR, CD4 and CD8 is expressed; T cell will then go through positive and negative selection to determine lineage

Question 48

What is a single positive T cell?

Answer 48

The cell expresses TCR and either CD4 or CD8

Question 49

What is positive selection in regards to T cells?

Answer 49

TCR binds MHC – peptide complexes in the thymus and only cells that express a TCR that can bind MHC-peptide complexes will be positively selected for

Question 50

What is negative selection in regards to T cells?

Answer 50

TCR binds MHC-peptide complexes in the thymus resulting in the elimination of autoreactive T cells; preventing production of disease causing T cells. This is determined by the strength of binding. Weak MHC binding will be selected for. Strong binding of MHC will result in T cell death

Question 51

What do NKT cells recognize?

Answer 51

These recognize glycolipids presented by CD1

Question 52

What do gamma/delta T cells recognize?

Answer 52

These recognize small molecules without MHC

Question 53

What is the first step in T cell maturation?

Answer 53

Early thymic progenitors migrate to the thymus

Question 54

After migrating to the thymus what is the next step in the maturation process?

Answer 54

Cells enter the thymus at the cortico-medullary junction and migrate through the cortex before moving to the medulla

Question 55

What happens to T cells in the cortex?

Answer 55

These mature from double negative to double positive T cells

Question 56

What occurs to T cells in the medulla?

Answer 56

These are selected to be CD4 or CD8 cells

Question 57

What is this an image of and what is each arrow pointing at?

Answer 57

This is an infants thymus. The top arrow is pointing at the lighter staining **medulla**, the middle arrow is pointing at the darker staining dense **cortex,** and the bottom arrow is the dense connective tissue **capsule** that surrounds the thymus.

Question 58

What is this an image of and what are the arrows pointing at?

Answer 58

This is an infant thymus, and the arrows are pointing at Hassall corpuscles.

Question 59

What is this an image of and what does each letter label?

Answer 59

This is an adult thymus. There is fewer lymphocytes present. CT = connective tissue; A = adipose tissue; and L = Lymphoid tissue.

Question 60

How would you describe this image of flow cytometry in T cell development?

Answer 60

This image displays a normal development of T cells

Question 61

This image shows what type of T cell development?

Answer 61

This is normal

Question 62

How would you describe this image in regards to T cell development?

Answer 62

Pt 1 - Pediatric T-cell acute lymphoblastic leukemia Most T-cells are double negative and have almost no CD3

Question 63

How would you describe this image in regards to T cell development?

Answer 63

Pediatric T-cell acute lymphoblastic leukemia have almost all double positive Lacks CD3 as well. Later even in T cell development may have gone awry.

Question 64

Lambda and kappa are two regions of what?

Answer 64

Light chains of BCRs